Lecithin-retinol Acyltransferase is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

Matthew L. Batten, Yoshikazu Imanishi, Tadao Maeda, Daniel Tu, Alexander R. Moise, Darin Bronson, Daniel Possin, Russell N. Van Gelder, Wolfgang Baehr, Krzysztof Palczewski

Research output: Contribution to journalArticle

246 Citations (Scopus)

Abstract

Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/- mouse develops normally. The histological analysis and electron microscopy of the retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are ∼35% shorter than those of Lrat+/+ mice, whereas other neuronal layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat-/- mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.

Original languageEnglish (US)
Pages (from-to)10422-10432
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number11
DOIs
StatePublished - Mar 12 2004
Externally publishedYes

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Knockout Mice
Liver
Esters
Vitamin A
Cones
Retinaldehyde
Rhodopsin
Retinoids
Chromophores
Gene expression
Pigments
Electron microscopy
Recycling
Animals
Blood
Rod Cell Outer Segment
Vertebrate Photoreceptor Cells
Tissue
Constriction
Genetic Recombination

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lecithin-retinol Acyltransferase is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver. / Batten, Matthew L.; Imanishi, Yoshikazu; Maeda, Tadao; Tu, Daniel; Moise, Alexander R.; Bronson, Darin; Possin, Daniel; Van Gelder, Russell N.; Baehr, Wolfgang; Palczewski, Krzysztof.

In: Journal of Biological Chemistry, Vol. 279, No. 11, 12.03.2004, p. 10422-10432.

Research output: Contribution to journalArticle

Batten, ML, Imanishi, Y, Maeda, T, Tu, D, Moise, AR, Bronson, D, Possin, D, Van Gelder, RN, Baehr, W & Palczewski, K 2004, 'Lecithin-retinol Acyltransferase is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver', Journal of Biological Chemistry, vol. 279, no. 11, pp. 10422-10432. https://doi.org/10.1074/jbc.M312410200
Batten, Matthew L. ; Imanishi, Yoshikazu ; Maeda, Tadao ; Tu, Daniel ; Moise, Alexander R. ; Bronson, Darin ; Possin, Daniel ; Van Gelder, Russell N. ; Baehr, Wolfgang ; Palczewski, Krzysztof. / Lecithin-retinol Acyltransferase is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 11. pp. 10422-10432.
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